Anaesthetic management of a patient with complex, cyanotic congenitally corrected transposition of great arteries for electrophysiological study and thermoablation.

Congenitally corrected transposition of great arteries (ccTGA) is a rare congenital heart disease, and little literature is available that describes its anaesthetic management. We present the perioperative management of a patient with complex, cyanotic ccTGA who underwent electrophysiological study with catheter ablation under general anaesthesia. Good understanding of the patient's complex cardiac anatomy and physiology and multidisciplinary communication are vital to facilitate the successful care of the patient.

Profound Hypoxemia From Right Ventricular Failure Following Acute Type A Aortic Dissection.

Acute aortic dissection is a catastrophic event with high mortality rate if left untreated. Complications of aortic dissection are fairly common, and some of them increase mortality rates further, necessitating early diagnosis and treatment. We present a case of Stanford type A aortic dissection with an uncommon complication of right ventricular failure, which resulted in a rare presentation of persistent hypoxemia despite intubation and maximal ventilatory support. Other common causes of hypoxemia were ruled out and this was eventually attributed to the aortic dissection and emergency surgery was arranged for the patient. Our case can help to increase the awareness of such a potential association, which should be considered in future similar clinical situations, thus minimizing any delay in management.

A graphene-based dengue immunosensor using plant-derived envelope glycoprotein domain III (EDIII) as the novel probe antigen.

The envelope glycoprotein domain III (EDIII) of dengue virus (DENV) has been recognised as the antigenic region responsible for receptor binding. In the present work, we have proposed a novel immunosensor constructed on a graphene-coated screen-printed carbon electrode (SPCE) using plant-derived EDIII as the probe antigen to target DENV IgG antibodies. The developed immunosensor demonstrated high sensitivity towards DENV IgG within a wide linear working range (125-2000 ng mL-1) under the optimised sensing conditions. The limit of detection was determined to be 22.5 ng mL-1. The immunosensor also showed high specificity towards DENV IgG, capable of differentiating DENV IgG from the antibodies of other infectious diseases including the similarly structured Zika virus (ZIKV). The ability of the immunosensor to detect dengue antibodies in serum samples was also verified by conducting tests on mouse serum samples. The proposed immunosensor was able to provide a binary (positive/negative) response towards the serum samples comparable to the conventional enzyme-linked immunosorbent assay (ELISA), indicating promising potential for realistic applications.

Regional economic development, household income, gender and hypertension: evidence from half a million Chinese.

BACKGROUND: Hypertension may be influenced by multiple factors, including social and individual determinants. Regional and individual economic disparity in China is closely associated with such factors that may give rise to diverse health outcomes. This study examines the relationship between regional economic development, household income, gender and hypertension prevalence in China. METHODS: This study utilized data from the China Kadoorie Biobank (CKB), a population-based study on half a million Chinese adults from 10 geographically distinct regions. Hypertension was identified by a measured systolic blood pressure/diastolic blood pressure ≥ 140/90 mmHg or receiving treatment. Regional economic development was inferred from GDP per capita at the time of the study. A logistic regression based method was used in calculating the prevalence of hypertension in different household income, regional economic development, and gender groups, adjusting for demographic, social-economic and lifestyle factors. RESULTS: The prevalence of hypertension was the lowest in the medium GDP per capita areas in both male (31.62, 95% CI: 31.26-31.98%) and female (22.85, 95% CI: 22.50-23.19%) as compared to that in the low GDP per capita regions (male: 32.75, 95% CI 32.41-33.08%; female: 32.12, 95% CI: 31.78-32.47%) and high GDP per capita areas (male: 39.74, 95% CI: 39.33-40.16%; female: 35.19, 95% CI: 34.74-35.65%). There was an inverse relationship between hypertension and household income in the low and high GDP areas and an U-shaped association in the medium GDP per capita areas. Higher hypertension prevalence was observed in males across all GDP per capita areas. The negative correlation between hypertension and household income (across all GDP per captia areas) was stronger in females than in males. CONCLUSIONS: The present study underlined the important influence of regional economic development, household income and gender on hypertension. Interventions for hypertension prevention and management should take into consideration the influence of sex difference and socioeconomic disparities at both micro- and macro- levels, in addition to a person-centered approach.

Association between maternal education and breast feeding practices in China: a population-based cross-sectional study.

OBJECTIVE: To investigate the association between maternal education and breast feeding in the Chinese population, with a consideration of household income and health-seeking behaviours. DESIGN: A nationally representative population-based cross-sectional study. SETTING: 77 counties from 12 geographically distinct regions in China. PARTICIPANTS: 10 408 mothers with children from 0 to 12 months of age, aged 15-53 years old (mean: 29.15, SD: 5.11) were classified into primary school or below group (n=781), middle school group (n=3842), high school/vocational school group (n=1990), college or above group (n=3795), according to their highest completed education. OUTCOMES: Five breastfeeding outcomes, including early initiation of breast feeding (EIB), exclusive breast feeding (EBF) under 6 months, predominant breast feeding under 6 months, current breast feeding and children ever breast fed, were calculated based on the standardised questionnaire from the WHO and Wellstart International's toolkit for monitoring and evaluating breastfeeding activities. RESULTS: The absolute risk of EIB and EBF in the lowest maternal education level was 64.85% and 26.53%, respectively, whereas the absolute risk of EIB and EBF in the highest maternal education level was 77.21% and 14.06%, respectively. A higher level of maternal education was positively associated with EIB (risk ratio (RR): 1.22; 95% CI: 1.12 to 1.30) and was inversely associated with EBF (RR: 0.59; 95% CI: 0.38 to 0.88). Stratified by household income, a positive association with EIB was observed only in the group with the highest household income and an inverse association with EBF was found in both low household and high household income groups. CONCLUSIONS: Mothers with a higher education were more likely to initiate early breast feeding when they were also from a high-income household while also being less likely to exclusively breast feed their babies. Routine and successful nursing is crucial for the health of infants and is influenced by maternal education. Future public health interventions to promote breast feeding should consider the issues related to the educational level of mothers.

FBXW5 Promotes Tumorigenesis and Metastasis in Gastric Cancer via Activation of the FAK-Src Signaling Pathway.

: F-box/WD repeat-containing protein 5 (FBXW5) is a member of the FBXW subclass of F-box proteins. Despite its known function as a component of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex, the role of FBXW5 in gastric cancer tumorigenesis and metastasis has not been investigated. The present study investigates the role of FBXW5 in tumorigenesis and metastasis, as well as the regulation of key signaling pathways in gastric cancer; using in-vitro FBXW5 knockdown/overexpression cell line and in-vivo models. In-vitro knockdown of FBXW5 results in a decrease in cell proliferation and cell cycle progression, with a concomitant increase in cell apoptosis and caspase-3 activity. Furthermore, knockdown of FBXW5 also leads to a down regulation in cell migration and adhesion, characterized by a reduction in actin polymerization, focal adhesion turnover and traction forces. This study also delineates the mechanistic role of FBXW5 in oncogenic signaling as its inhibition down regulates RhoA-ROCK 1 (Rho-associated protein kinase 1) and focal adhesion kinase (FAK) signaling cascades. Overexpression of FBXW5 promotes in-vivo tumor growth, whereas its inhibition down regulates in-vivo tumor metastasis. When considered together, our study identifies the novel oncogenic role of FBXW5 in gastric cancer and draws further interest regarding its clinical utility as a potential therapeutic target.

Interplay of regional economic development, income, gender and type 2 diabetes: evidence from half a million Chinese.

BACKGROUND: Following the rapid economic growth, there has been a strong disparity of regional development and personal income in China. Type 2 diabetes mellitus (T2DM) may be influenced by socioeconomic status at both the societal and individual levels. This study examines the associations of regional economic development, household income and gender on T2DM. METHOD: Data from the baseline of a Chinese population-based study of approximately 500 000 adults from 10 areas were analysed. Clinically identified and screen-detected T2DM were examined. Regional economic development was indicated by gross domestic product (GDP) per capita. A logistic regression-based method was used to calculate the adjusted prevalence. RESULT: The prevalence of T2DM was significantly higher in medium GDP per capita areas for both males (7.04%, 95% CI 6.82% to 7.26%) and females (6.04%, 95% CI 5.86% to 6.22%) compared with areas of other levels of economic development. The different shapes of associations between household income and T2DM prevalence were observed in different GDP per capita areas. There were strong gender differences in terms of both the trend and strength of association between household income and T2DM prevalence. CONCLUSIONS: Findings from this study underscore the importance of economic conditions and gender difference on T2DM. It suggests that strategies for diabetes prevention should address social-economic differences besides a person-centred approach.

Recruitment and significance of Th22 cells and Th17 cells in malignant ascites.

T helper (Th)22 and Th17 cells are implicated in the pathogenesis of a number of types of cancer. However, the function of Th22 and Th17 cells in malignant ascites (MA) remains unknown. The present study aimed at examining the distribution, phenotypes, recruitment, and prognostic value of Th22 and Th17 cells in MA from patients with hepatocellular carcinoma (HCC). A total of 26 patients with HCC with MA and 15 healthy controls were included in the present study. The proportion of Th22 cells, Th17 cells, C-C motif chemokine receptor (CCR)4, CCR6 and CCR10 were examined using flow cytometry. Interleukin (IL-)22, IL-17, C-C motif chemokine ligand (CCL)20, CCL22 and CCL27 were investigated using ELISA. In addition, the chemoattractant activity of chemokines for Th22 and Th17 cells in vitro were examined via a chemotaxis assay. The results of the present study demonstrated that Th22 cells, Th17 cells, IL-22 and IL-17 were significantly increased in MA compared with the corresponding blood and peripheral blood from healthy controls. Additionally, Th22 cells expressed increased concentrations of CCR6, CCR4 and CCR10, and Th17 cells expressed increased concentrations of CCR4 and CCR6 in MA compared with the corresponding blood. The chemotaxis assay revealed that CCL20/CCR6, CCL22/CCR4 and CCL27/CCR10 were responsible for the recruitment of Th22 cells into MA, whereas CCL22/CCR4 was responsible for the recruitment of Th17 cells. Furthermore, the patients with an increased number of Th17 cells exhibited an increased survival time compared with patients with a limited number of Th17 cells. Th22 and Th17 cells serve an important function in the development of MA, and the accumulation of Th22 and Th17 cells in MA may be due to a local increase in proinflammatory cytokines and chemokines. Increased Th17 cell numbers in MA may indicate the improvement of patient survival.

Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor.

Exportin-1 (XPO1) controls the nucleo-cytoplasmic trafficking of several key growth regulatory and tumor suppressor proteins. Nuclear export blockade through XPO1 inhibition is a target for therapeutic inhibition in many cancers. Studies have suggested XPO1 upregulation as an indicator of poor prognosis in gastric cancer. In the current study, we investigated the anti-tumor efficacy of selective inhibitors of nuclear export (SINE) compounds KPT-185, KTP-276 and clinical stage selinexor (KPT-330) in gastric cancer. XPO1 was found to be overexpressed in gastric cancer as compared to adjacent normal tissues and was correlated with poor survival outcomes. Among the 3 SINE compounds, in vitro targeting of XPO1 with selinexor resulted in greatest potency with significant anti-proliferative effects at nano molar concentrations. XPO1 inhibition by selinexor resulted in nuclear accumulation of p53, causing cell cycle arrest and apoptosis. Also, inhibition of XPO1 lead to the cytoplasmic retention of p21 and suppression of survivin. Orally administered selienxor caused significant inhibition of tumor growth in xenograft models of gastric cancer. Furthermore, combination of selinexor with irinotecan exhibited greater anti-tumor effect compared to individual treatment. Taken together, our study underscores the therapeutic utility of XPO1 targeting in gastric cancer and suggests the potential benefits of XPO1 inhibition in-combination with chemotherapy.

Real-Time Tumor Gene Expression Profiling to Direct Gastric Cancer Chemotherapy: Proof-of-Concept "3G" Trial.

Purpose: The oxaliplatin plus S-1 and cisplatin plus S-1 regimens are interchangeably used in the management of advanced gastric cancer. The previously reported G-intestinal (G1) and G-diffuse (G2) intrinsic gene expression signatures showed promise for stratifying patients according to their tumor sensitivity to oxaliplatin or cisplatin.Experimental Design: The proof-of-concept, multicenter, open-label phase II "3G" trial was done to prospectively evaluate the feasibility and efficacy of using genomic classifiers to tailor treatment in gastric cancer. Patients' tumors were classified as "G1" or "G2" using a nearest-prediction template method, or "G3" (unclear assignment) when FDR ≥ 0.05. The first 30 patients in the "G1" cohort were assigned oxaliplatin plus S-1 (SOX) chemotherapy; thereafter, subsequently recruited "G1" patients were treated with cisplatin plus S-1 (SP) chemotherapy. "G2" patients and "G3" patients were treated with SP and SOX chemotherapy, respectively.Results: A total of 48, 21, and 12 patients, respectively, were given "G1," "G2," and "G3" genomic assignments. Median turnaround time was 7 days (IQR, 5-9). Response rates were 44.8%, 8.3%, 26.7%, and 55.6% for the "G1-SOX," "G1-SP," "G2," "G3" cohorts, respectively; and was higher in G1 patients treated with SOX compared with SP (P = 0.033). Exploratory analyses using the genomic classifier of Lei and colleagues validated the utility of the metabolic signature as a biomarker for predicting benefit from chemotherapy (log-rank P = 0.004 for PFS), whereas the Asian Cancer Research Group classifier did not demonstrate any predictive value.Conclusions: This bench-to-bedside effort establishes a reasonable turnaround time for gene expression profiling and possible utility of genomic classifiers in gastric cancer treatment stratification. Clin Cancer Res; 24(21); 5272-81. ©2018 AACR.

ATM Expression Predicts Veliparib and Irinotecan Sensitivity in Gastric Cancer by Mediating P53-Independent Regulation of Cell Cycle and Apoptosis.

Identification of synthetically lethal cellular targets and synergistic drug combinations is important in cancer chemotherapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signaling and cell-cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its implications as a predictive biomarker for cancer chemotherapy remain unexplored. The present study evaluated ATM-induced synthetic lethality and its role in sensitization of gastric cancer cells to PARP and TOP1 inhibitors, veliparib (ABT-888) and irinotecan (CPT-11), respectively. ATM expression was detected in a panel of gastric cell lines, and the IC50 against each inhibitors was determined. The combinatorial effect of ABT-888 and CPT-11 in gastric cancer cells was also determined both in vitro and in vivo ATM deficiency was found to be associated with enhanced sensitivity to ABT-888 and CPT-11 monotherapy, hence suggesting a mechanism of synthetic lethality. Cells with high ATM expression showed reduced sensitivity to monotherapy; however, they showed a higher therapeutic effect with ABT-888 and CPT-11 combinatorial therapy. Furthermore, ATM expression was shown to play a major role in cellular homeostasis by regulating cell-cycle progression and apoptosis in a P53-independent manner. The present study highlights the clinical utility of ATM expression as a predictive marker for sensitivity of gastric cancer cells to PARP and TOP1 inhibition and provides a deeper mechanistic insight into ATM-dependent regulation of cellular processes. Mol Cancer Ther; 15(12); 3087-96. ©2016 AACR.

Melanoma associated antigen (MAGE)-A3 promotes cell proliferation and chemotherapeutic drug resistance in gastric cancer.

BACKGROUND: Melanoma-associated antigen (MAGE)-A3 is a member of the family of cancer-testis antigens and has been found to be epigenetically regulated and aberrantly expressed in various cancer types. It has also been found that MAGE-A3 expression may correlate with an aggressive clinical course and with chemo-resistance. The objectives of this study were to assess the relationship between MAGE-A3 promoter methylation and expression and (1) gastric cancer patient survival and (2) its functional consequences in gastric cancer-derived cells. METHODS: Samples from two independent gastric cancer cohorts (including matched non-malignant gastric samples) were included in this study. MAGE-A3 methylation and mRNA expression levels were determined by methylation-specific PCR (MSP) and quantitative real-time PCR (qPCR), respectively. MAGE-A3 expression was knocked down in MKN1 gastric cancer-derived cells using miRNAs. In addition, in vitro cell proliferation, colony formation, apoptosis, cell cycle, drug treatment, immunohistochemistry and Western blot assays were performed. RESULTS: Clinical analysis of 223 primary patient-derived samples (ntumor = 161, nnormal = 62) showed a significant inverse correlation between MAGE-A3 promoter methylation and expression in the cancer samples (R = -0.63, p = 5.99e-19). A lower MAGE-A3 methylation level was found to be associated with a worse patient survival (HR: 1.5, 95 % CI: 1.02-2.37, p = 0.04). In addition, we found that miRNA-mediated knockdown of MAGE-A3 expression in MKN1 cells caused a reduction in its proliferation and colony forming capacities, respectively. Under stress conditions MAGE-A3 was found to regulate the expression of Bax and p21. MAGE-A3 knock down also led to an increase in Puma and Noxa expression, thus contributing to an enhanced docetaxel sensitivity in the gastric cancer-derived cells. CONCLUSIONS: From our results we conclude that MAGE-A3 expression is regulated epigenetically by promoter methylation, and that its expression contributes to gastric cell proliferation and drug sensitivity. This study underscores the potential implications of MAGE-A3 as a therapeutic target and prognostic marker in gastric cancer patients.

Outcome of Single-Bundle Hamstring Anterior Cruciate Ligament Reconstruction Using the Anteromedial Versus the Transtibial Technique: A Systematic Review and Meta-analysis.

PURPOSE: To compare the clinical outcomes of single-bundle hamstring anterior cruciate ligament (ACL) reconstruction between the anteromedial (AM) and transtibial (TT) techniques. METHODS: We performed a comprehensive systematic review and meta-analysis of the English-language literature in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases for articles that compared clinical outcomes of AM versus TT ACL reconstruction. The outcome measures analyzed included postoperative Lachman test, pivot-shift test, International Knee Documentation Committee (IKDC), and Lysholm scores. RESULTS: We included 10 articles from an initial 308 abstracts for the systematic review and included 6 studies for the meta-analysis. The study population consisted of a total of 733 patients, of whom 366 (49.9%) underwent the AM technique and 367 (50.1%) underwent the TT technique for ACL reconstruction. For postoperative knee stability, the AM technique yielded superior results in terms of the proportion of negative Lachman test results (n = 243; odds ratio [OR], 2.98 [95% confidence interval (CI), 1.29 to 6.88]) and proportion of negative pivot-shift test results (n = 238; OR, 3.67 [95% CI, 1.80 to 7.52]). For postoperative functional status, the AM technique yielded superior results in terms of objective IKDC grading (proportion with IKDC grade A) (n = 269; OR, 2.19 [95% CI, 1.23 to 3.88]) but had comparable Lysholm scores (n = 478; mean difference, 1.43 [95% CI, 0.01 to 2.84]). CONCLUSIONS: Single-bundle hamstring ACL reconstruction using the AM technique showed superior surgeon-recorded stability according to the IKDC knee score, Lachman test, and pivot-shift test. However, there was no difference in patient-reported functional outcome (Lysholm score). LEVEL OF EVIDENCE: Level III, systematic review and meta-analysis of Level I, II, and III studies.

GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells.

BACKGROUND: Platinum based therapy is commonly used in the treatment of advanced gastric cancer. However, resistance to chemotherapy is a major challenge that causes marked variation in individual response rate and survival rate. In this study, we aimed to identify the expression of GTSE1 and its correlation with cisplatin resistance in gastric cancer cells. METHODS: Methylation profiling was carried out in tissue samples from gastric cancer patients before undergoing neoadjuvent therapy using docetaxel, cisplatin and 5FU (DCX) and in gastric cancer cell lines. The correlation between GTSE1 expression and methylation in gastric cancer cells was determined by RT-PCR and MSP respectively. GTSE1 expression was knocked-down using shRNA's and its effects on cisplatin cytotoxicity and cell survival were detected by MTS, proliferation and clonogenic survival assays. Additionally, the effect of GTSE1 knock down in drug induced apoptosis was determined by western blotting and apoptosis assays. RESULTS: GTSE1 exhibited a differential methylation index in gastric cancer patients and in cell lines that correlated with DCX treatment response and cisplatin sensitivity, respectively. In-vitro, GTSE1 expression showed a direct correlation with hypomethylation. Interestingly, Cisplatin treatment induced a dose dependent up regulation as well as nuclear translocation of GTSE1 expression in gastric cancer cells. Knock down of GTSE1 enhanced cisplatin cytotoxity and led to a significant reduction in cell proliferation and clonogenic survival. Also, loss of GTSE1 expression caused a significant increase in P53 mediated apoptosis in cisplatin treated cells. CONCLUSION: Our study identifies GTSE1 as a biomarker for cisplatin resistance in gastric cancer cells. This study also suggests the repressive role of GTSE1 in cisplatin induced apoptosis and signifies its potential utility as a therapeutic target for better clinical management of gastric cancer patients.